Crosslinked and Polymerized Hemoglobins as Potential Blood Substitutes

Olsen, Kenneth W.; Tarasov, Eugene

doi:10.1002/9781119975427.ch24

Cited by 1 publication

(1 citation statement)

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“…Hemoglobin- (Hb-) based oxygen (O 2 ) carriers (HBOCs) are a promising class of red blood cell (RBC) substitute currently undergoing development as an O 2 therapeutic. Currently, many methods of HBOC preparation are being explored, including protein polymerization, − surface conjugation with polyethylene glycol, , liposome encapsulation, − microparticle formulation, , and the recombinant expression of genetically modified Hb . Because of the low cost of polymerization reagents, the polymerization of Hb with the chemical cross-linker glutaraldehyde to form polymerized Hb (PolyHb) is the most common strategy for manufacturing HBOCs for use as RBC substitutes in transfusion medicine.…”

Section: Introductionmentioning

confidence: 99%

Controlled Polymerization and Ultrafiltration Increase the Consistency of Polymerized Hemoglobin for Use as an Oxygen Carrier

et al. 2019

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Polymerized human hemoglobins (PolyhHbs) are a promising class of red blood cell substitute for use in transfusion medicine. Unfortunately, the application of the commonly used glutaraldehyde cross-linking chemistry to synthesize these materials results in a complex mixture of PolyhHb molecules with highly varied batch-to-batch consistency. We implemented a controlled method of gas exchange and reagent addition that results in a homogeneous PolyhHb product. A fully coupled tangential flow filtration system was used to purify and concentrate the synthesized PolyhHb molecules. This improved method of PolyhHb production could be used to more precisely control the size and reduce the polydispersity of PolyhHb molecules, with minimal effects on the resulting oxygen-carrying capability. In addition to these factors, we assessed how the hemoglobin scavenging protein haptoglobin (Hp) would interact with PolyhHb molecules of varying sizes and quarternary states. Our results indicated that T-state PolyhHbs may be more efficiently detoxified by Hp compared with R-state PolyhHb and unmodified Hb.

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